Method and apparatus for skin absorption enhancement and transdermal drug delivery

ABSTRACT

Application of electrical pulses is made in a controlled manner, in order to increase the absorption of substances applied previously on the skin. Optionally, mechanical vibrations may also be provided to the skin to increase the absorption effect. The electrical pulses are provided to the skin by way of an array of electrodes disposed on a vibrating head plate, and the mechanical vibrations are provided to the skin by way of the vibrating head plate being made to vibrate (if that option is utilized). Preferably, the electrical and mechanical vibrations are at the same frequency and phase with respect to each other, in order to increase the absorption effect. Also, at the same time the electrical pulses are provided to the skin, a syringe containing a skin enhancement substance or a drug is actuated so as to move a particular amount of the substance from the skin, whereby the substance is passed through a tube and then into a groove surrounding a central electrode of the array of electrodes disposed on the plate. The substance is absorbed within the skin as a result.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application claims priority to U.S. Provisional Application No.60/281,808, filed Apr. 6, 2001, and whereby this application is acontinuation-in-part of U.S. patent application Ser. No. 10/074,234,filed Feb. 14, 2002 pending, which in turn is a continuation-in-part ofU.S. patent application Ser. No. 09/942,044, filed Aug. 30, 2001 nowU.S. Pat. No. 6,687,537, which in turn is a continuation-in-part of U.S.patent application Ser. No. 09/922,927, filed Aug. 7, 2001 now U.S. Pat.No. 6,535,761, each of which is incorporated in its entirety herein byreference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to application of electrical pulses and mechanicalvibrations to the skin in a controlled manner, in order to increase theabsorption of a substance that is applied at the same time to the skinby way of a syringe.

2. Description of the Related Art

It is known that an electrical pulse applied to the skin is useful inorder to increase the absorption of a substance previously applied tothe skin, whereby this technique is known as electroporation. Such asubstance to be applied to the skin may be a liquid, a gel, a lotion, ora cream, for example.

It is desired to provide an apparatus and a method to increase theabsorption of a substance to be applied to the skin, in order to obtainan increased (e.g., moisturizing) affect of the substance applied to theskin.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus and a method forenhancing the absorption of a substance to be applied on the skin.

To accomplish this, the present invention uses a sequence of electricalpulses (between 20 and 200V peak to peak, preferably, and between 50 and15,000 Hz preferably) provided to electrodes that are placed in contactwith the skin. There is also provided a corresponding surface vibrationto the skin, by application of a mechanical vibration to the skin. Themechanical vibration is preferably of the same frequency and phase asthe electrical pulses applied to the skin. The mechanical vibration isprovided by way of a vibrating plate that also contains the electrodes(which provide the electrical stimulus to the skin at the same time themechanical vibration is provided to the skin). In an alternativeconfiguration, only electrical pulses are provided to the skin, wherebymechanical vibrations are not utilized.

The substance to be absorbed by the skin is applied to the skin by wayof a syringe, which outputs the substance by way of a tube that isconnected to an output of the syringe at one end of the tube and wherethe other end of the tube is disposed adjacent to a groove (or trough)surrounding a central electrode of an array of electrodes. Such asubstance that is provided to the skin may be a cream, liquid or gel(for example, collagen, or cocoa butter, or suntan oil, or other typesof skin enhancement lotions), or a drug to be administered into theskin.

The method according to an embodiment of the invention includes:

1) An apparatus which includes the following elements to perform thefollowing treatment:

a) a probe having an array of electrodes on a head portion of the probe,with a central electrode disposed at a central location on the headportion and with a plurality of circumferential electrodes disposedaround the central electrode.

b) a pulse generator connected to the array of electrodes.

c) a vibrator which vibrates the head portion of the probe at a sametime the electrical pulses are provided to the array of electrodes onthe head portion.

d) a syringe that provides a substance to the skin under control of amotor that outputs the substance from the syringe in a controlledmanner, whereby the substance is provided to a groove or trough thatsurrounds the central electrode.

During operation, as electrical pulses are provided to the skin by wayof the electrodes on the head of the probe, and, at the same time,mechanical vibrations are provided to the skin by way of the vibratinghead portion, the substance disposed within the trough surrounding thecentral electrode is absorbed within the skin due to the skin poresopening up as a result of the electrical pulses and mechanicalvibrations being applied to the skin. Alternatively, only electricalpulses are provided to the skin, which does not provide as good a skinabsorption effect as using both electrical pulses and mechanicalvibrations.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing advantages and features of the invention will becomeapparent upon reference to the following detailed description and theaccompanying drawings, of which:

FIG. 1A is a side view of a vibration mechanism that is disposed withinan apparatus according to the present invention;

FIG. 1B is a front view of the vibration mechanism of FIG. 1A;

FIG. 2A shows an array of electrodes provided on an outer surface of thevibration plate that faces the skin, according to a first embodiment ofthe invention;

FIG. 2B shows an array of electrodes provided on an outer surface of thevibration plate that faces the skin, according to a second embodiment ofthe invention;

FIG. 2C shows an array of electrodes provided on an outer surface of thevibration plate that faces the skin, according to a third embodiment ofthe invention;

FIG. 3 shows a side view of a head of a probe that is used to provideboth electrical and mechanical stimulation to the skin, in order to havea substance previously applied to the skin to be absorbed better,according to the invention;

FIG. 4 shows an electrical diagram of a pulse generator that provideselectrical pulses to an array of electrodes disposed on a vibratingplate provided at a head-end of the probe, according to one possibleconfiguration of an apparatus according to the invention;

FIG. 4A shows a train of square-wave pulses that are input to the pulsegenerator of FIG. 4;

FIG. 4B shows a train of exponential pulses that are output from thepulse generator of FIG. 4;

FIG. 5 shows one configuration of a hand-held probe that is used toprovide both electrical and mechanical stimulation to the skin,according to one or more embodiments of the invention;

FIG. 6 shows a current generator connection according to a fourthembodiment of the invention;

FIG. 7 shows elements provided at the head portion of a probe, accordingto a fifth embodiment of the invention; and

FIG. 8 shows a front view of the head portion of the probe according tothe fifth embodiment of the invention;

FIG. 9 shows a front view of the head portion of the probe according toan eighth embodiment of the invention;

FIG. 10 shows a first section view of the head portion of the probeaccording to the eighth embodiment of the invention, whereby suction isnot being applied to the skin;

FIG. 11 shows a second section view of the head portion of the probeaccording to the eighth embodiment of the invention, in which suction isbeing applied to the skin;

FIG. 12 shows a structure of an electroporation device according to aninth embodiment of the invention;

FIG. 13 shows components used to couple electrodes and wires to a headof the electroporation device according to the ninth embodiment of theinvention;

FIG. 14 shows a side view of the head of a probe used in an apparatusaccording to the ninth embodiment of the invention;

FIG. 15 shows a back view of the head of a probe, along withtransformers shown, in an apparatus according to a tenth embodiment ofthe invention;

FIG. 16 shows a front view of the head of a probe used in an apparatusaccording to the tenth embodiment of the invention;

FIG. 17 shows a front view of the head of a probe having threeelectrodes, which is used in an apparatus according to an eleventhembodiment of the invention;

FIG. 18 shows a back view of the head of a probe having threeelectrodes, along with transformers providing electronic pulses to thethree electrodes, which is used in an apparatus according to theeleventh embodiment of the invention; and

FIG. 19 shows staggered square-wave input pulses and exponential outputspulses with respect to the three transformers which is used in anapparatus according to the eleventh embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Preferred embodiments of the invention will be described in detailbelow, with reference to the accompanying drawings.

Based on experimental tests on the skin, it has been found by theinventor that after one or more pulses are applied between two points onthe skin, transpiration (or absorption) in the area between the twopoints on the skin increases. The pulses that give optimal results areexponential pulses that are generated by a charged capacitor that isdischarged on at least two separate points on the skin.

These experimental results have been utilized by the inventor in orderto develop an apparatus and method that maintains the transpiration ofthe skin at a high level, so that the skin can readily absorb a gel,liquid, lotion, cream, or drug that is applied to the skin. The drug maybe used to treat skin melanoma and/or cancerous tumors located justbelow the skin surface, for example.

The apparatus according to an embodiment of the present inventionapplies a sequence of pulses over an area or skin, by using an array ofelectrodes that are placed in contact with the skin. The array ofelectrodes are provided on a vibrating plate at the head of a probe,such as a hand-held probe 500 as shown in FIG. 5. The array ofelectrodes may be a configured as shown in FIG. 2A in a firstembodiment, whereby odd rows of electrodes are electrically connected toeach other, and thereby to a first output of a pulse generator 400 (seealso FIG. 4) via a first electrical connection. The even rows ofelectrodes are electrically connected to each other, and also to asecond output of the pulse generator 400 via a second electricalconnection. The array of electrodes on the vibrating plate mayalternatively be configured as shown in FIG. 2B in a second embodiment,whereby odd rows of round electrodes are electrically connected to eachother, and thereby to the first output of the pulse generator 400 via afirst electrical connection. The even rows of round electrodes areelectrically connected to each other, and thereby to the second outputof the pulse generator 400 via a second electrical connection.

The increase of the transpiration of the skin that is obtained by way ofthe present invention has the effect of increasing the absorption ofliquids, creams, lotions, gels, or skin treatment drugs (or other kindsof drugs) that have been previously provided on the skin in the areabetween where the electrodes are applied to the skin.

The electrical pulses that are applied on the skin in order to enhancethe transpiration of the skin are pulses obtained by a discharge of acapacitor on the skin. A square-wave pulse input to a primary winding ofthe transformer 410 of FIG. 4, with an output of the secondary windingof the transformer 410 being coupled to the skin by way of theelectrodes, provides the same effect as a discharging capacitor. Theexponential pulses are generated during the rising edge and falling edgeof each square-wave input pulse that is input to the transformer 410from a square-wave pulse generator, and have opposite sign (positiveexponential pulse due to the rising edge of a square-wave input pulse,negative exponential pulse due to the falling edge of the samesquare-wave input pulse). With the use of such a pulse generator 400 asshown in FIG. 4, it is possible to apply a burst of separate pulses(e.g., 500 to 1500 per second) to the skin, with adjacent pulses beingof opposite polarity and which provides a transpiration effect betterthan just providing one pulse or many pulses of the same polarity to theskin.

Switching transistor 430 provides square-wave pulses as shown in FIG. 4Ato the primary winding of the transformer 410, as shown in FIG. 4. Thepulses generated by the pulse generator 400 of FIG. 4, when the load isa pure resistance (or inductive or other type of reactive load), is asequence of exponential decay pulses of opposite symmetrical polarities,as shown in FIG. 4B. Such a circuit that includes the pulse generator400 provides an excellent coupling to the impedance of the skin.Moreover, the inductance of the transformer 410 together with thecapacitance of the skin generates a resonant circuit, which is desirableto achieve an opening of the skin pores or membranes.

The voltage waveform is conveniently modified when applied to the skindue to the fact that the electrical equivalent circuit of the skin is aresistance and a capacitance in parallel. The resulting voltage waveformhas a longer rise time (due to the RC time constant), and is dependentupon the capacitance of the skin, while maintaining the same peakcurrent and the same exponential decay waveform.

Such a circuit according to the first embodiment gives an advantage incomparison to traditional pulse generators that deliver pulses of apredefined value and shape of tension or current. By way of the presentinvention according to the first embodiment, it is possible to deliverhigher energy value per pulse, and also at the same time avoid possibledamage to the skin that would occur if high current amounts were appliedto the skin. The circuit utilized in the first embodiment self adjuststhe value of the current, tension and waveform shape. In particular, theimpedance of the skin decreases after the first pulse is applied to theskin. In this way, the voltage of the first pulse is higher thansubsequent pulses, since the impedance of the skin is higher at the timethe first pulse is applied to the skin. The voltage of the second andfollowing pulses applied to the skin decreases with the decreasing ofthe impedance of the skin, while maintaining the peak current at thesame or almost the same value.

Typical values of current and tension are provided herein. Case 1: loadimpedance of 10 kohm, peak voltage of 100 V, peak current of 10milliamperes, pulse width of 220 microseconds. Case 2: load impedance of1 kohm, peak voltage of 10 V, peak current of 10 milliamperes, pulsewidth of 220 microseconds. The pulses are preferably delivered inbursts, where the burst rate is the same as the mechanical vibrationrate. A typical value of the burst rate (and mechanical rate) is between40 Hz and 100 Hz.

Normally, when a square wave is applied to the skin, due to thecapacitive effect of the skin, it is possible to obtain about a threemicrosecond time constant exponential decay current. This is whathappens when a square wave voltage is applied to a circuit thatcorresponds to a resistor in parallel with a capacitor.

With such a circuit, only the peak current is enhanced, charging to amaximum allowable voltage the skin capacitance by applying an electricalenergy equal to the magnetic energy of the transformer 410. This effectmost likely provides for the opening of the cell membranes or pores ofthe skin (to achieve the transpiration effect) only during the time wheneach pulse is applied to the skin.

The effect of applying the probe to the skin is that the skin vibratesdue to the electrical pulses applied by way of the array of electrodes.The electrical pulses are preferably applied at a fixed frequencybetween 200 and 10,000 Hz (optimally at a frequency value between 2,500to 3,000 Hz), and are grouped in a burst. The ON time of each burst is afixed value between 5 to 50 milliseconds, and the OFF time between twoconsecutive bursts is a fixed value between 5 to 50 milliseconds (thepreferred burst ON time is 10 milliseconds and the preferred OFF timebetween consecutive bursts is 10 milliseconds).

As described above, the electrical pulses applied to the skin by way ofthe electrodes are preferably exponential pulses with peak-to-peakvoltage of 160 V at a fixed frequency between 2,500 to 3,000 Hz. One wayof providing such electrical pulses is by an electrical structure thatcorresponds to a pulse generator 400 as shown in FIG. 4, in which atransformer 410 is used as an element of the pulse generator 400.

The transformer 410, as well as the other elements of the pulsegenerator 400, are preferably housed within the probe 500 of FIG. 5.

Referring back to FIG. 4, the primary winding 420 of the transformer 410is driven by a transistor 430 that is switched on and off, and thesecondary winding 440 of the transformer 410 is directly applied to thearray of electrodes (see FIG. 1A or 1B) with an electrical resistance450 provided therebetween. The electrical resistance 450 may be 200 Kohmor some value in that range (e.g., 100 Kohm to 500 Kohm), and isprovided in order to avoid high voltages when the array of electrodesare not applied to the skin, so that in that case it operates as an opencircuit. In such a situation, the peak-to-peak voltage is 400 V orthereabouts.

Along with the electrical pulses applied to the skin, a mechanicalvibration is also provided to the skin in the first embodiment in orderto increase the absorption of a substance that is applied on the skin.

The absorption effect is enhanced by the simultaneous increase oftranspiration, whereby the absorption effect is greatest when themechanical vibration is synchronized in phase and in frequency with theelectric pulse application. Thus, in the example discussed above, whilethe electrical burst of pulses (at 2,200 Hz) are provided to the skin ata burst ON/OFF frequency, e.g., 50 Hz, by way of an electrode array, theskin is also mechanically vibrated at the same frequency, e.g., 50 Hz,by way of the vibrating plate. The mechanical vibration and theelectrical burst application are also preferably provided in phase withrespect to each other, in order to increase the skin absorption effect.There are several well known ways to achieve this frequency and phasesynchronization. In the preferred embodiments described herein, anoptical sensor (not shown) detects the movement of the eccentric of amotor that is used to provide the mechanical vibrations (see FIGS. 1Aand 1B, for example), and gates the burst of electrical pulses based onthe detected movement.

Thus, in the example discussed above, while the burst of electricalpulses are provided to the skin by way of the electrode array, the skinis also mechanically vibrated at the same frequency by way of thevibrating plate. The mechanical vibration and electrical pulseapplication is also preferably provided in phase with respect to eachother, in order to increase the skin absorption effect.

Moreover, the absorption effect is further enhanced when the mechanicalvibration is applied orthogonal to the surface of the skin. WhileApplicant does not intend to be tied down to any particular theory ofoperation, one possible explanation of the physical phenomena of one ormore embodiments of the present invention is that, while the electricalpulses “stretch” the skin, thus increasing periodically the diameter ofthe pores of the skin, at the same time the mechanical vibration “pumps”the substances (gel, liquid or cream) inside the skin (through theopened pores). The mechanical and electrical synchronization achievesthe effect that the “pumping” action (due to the mechanical stimulationof the skin) takes place at the same instant in time that the pores areat their maximum “open” diameter (due to the electrical stimulation ofthe skin).

The apparatus according to a first embodiment the present inventionincludes a probe having two main parts:

A) a handle containing a power source (e.g., batteries) and a pulsegenerator; and

B) a vibrating head containing components for generating the vibrationand also containing an array of electrodes.

The vibrating head, in a preferred configuration, includes a D.C.electrical motor for generating vibrations to the skin. FIGS. 1A and 1Bshow two different views of the D.C. electrical motor 110, the rotatingshaft of the D.C. electrical motor 110 is an eccentric 120 to therebyprovide eccentric motion. The eccentric motion, during rotation of theD.C. electrical motor 110, generates a vibration onto the vibratingplate 130 (that is directly coupled to the D.C. electrical motor 110)that is at the same frequency of the rotation of the D.C. electricalmotor 110 (e.g., 50 Hz or 60 Hz or some other desired frequency). Otherways of causing vibrations in synchronization with the providing ofelectrical pulses to a patient may be contemplated while remainingwithin the scope of the invention.

As explained earlier, FIG. 4 shows circuitry for providing electricalpulses to the array of electrodes shown in FIGS. 2A and 2B. Thecircuitry of FIG. 4 corresponds to a pulse generator 400, and ispreferably disposed within the housing of the probe 500 of FIG. 5. Theelectrical pulses generated by the pulse generator 400, when thosepulses are provided to the skin, preferably are exponential pulses withpeak-to-peak voltage of 160 V at a frequency of between 2,500 Hz to3,000 Hz. Of course, other peak-to-peak voltage values (e.g., 100 V to200 V) and operating frequencies (50 Hz to 15,000 Hz) may be employed,while remaining within the scope of the invention as described herein.Alternatively, sawtooth or sinusoidal pulses may be provided to theelectrodes, but exponential pulses appear to provide better skintranspiration results.

FIGS. 1A and 1B show the vibrating plate 130 that is physically coupledto the D.C. electrical motor 110. The vibrating plate 130 preferably is50×50 mm in size (other sizes are possible while remaining within thescope of the invention), where parallel metallic stripes are depositedon it as shown in FIG. 2A, in order form the array of electrodes. Thevibrating plate 130 is caused to vibrate at the same phase and frequencyas the electrical pulses provided to the skin by way of the array ofelectrodes (disposed on the vibrating plate), in order to enhance theskin absorption effect.

As shown in FIG. 2A, which shows a first embodiment of an electrodearray 210 that is provided on a skin-side surface of the vibrating plate130, five parallel metallic stripes 220 are provided, each preferably ofa size of 50 mm×4 mm. Each of the five electrodes 220 are preferably 6mm apart from adjacently-positioned electrodes. The electrodes 220 arealternately electrically connected (e.g., the first, third and fifth roware electrically connected to each other by way of electrical line 250;and the second and fourth rows are electrically connected to each otherby way of electrical line 260). Other electrode array configurations arepossible while remaining within the scope of the invention, such havinga number of electrodes greater than two, such as having seven or eightelectrodes.

FIG. 2B shows a second embodiment of an electrode array that is providedon a skin-side surface of a vibration plate. In FIG. 2B, there areprovided 25 round electrodes 230 each of 4 mm diameter, each separatedat least 6 mm from adjacently-positioned round electrodes. The roundelectrodes 230 are alternately electrically connected to each other(e.g., the electrodes on the first, third and fifth rows areelectrically connected to each other by way of electrical line 270; andthe electrodes on the second and fourth rows are electrically connectedto each other by way of electrical line 280). The spacing between theelectrodes 230 shown in FIG. 2B may vary between 1 to 20 mm and the sizeof each of the electrodes 230 may vary between 1 to 20 mm in diameter.

FIG. 2C shows an array of electrodes provided on an outer surface of thevibration plate that faces the skin, according to the third embodimentof the invention. In FIG. 2C, there are provided electrodes 233 that aredisposed on the periphery of the vibration plate, which are electricallycoupled to each other, and which are electrically coupled to a firstoutput of the pulse generator 400 by way of a first electricalconnection 235. In FIG. 2C, there is also provided acentrally-positioned electrode 237, which is not electrically coupled toany other of the electrodes, and which is electrically coupled to asecond output of the pulse generator 400 by way of a second electricalconnection 239.

FIG. 3 shows a side view of a vibrating head 310 of a probe that is usedto provide both electrical and mechanical stimulation to the skinaccording to an embodiment of the present invention, in order to have asubstance previously applied to the skin be absorbed better. As shown inFIG. 3, the vibrating head 310 includes the array of electrodes 320provided on a skin-side surface thereof. The array of electrodes 320 maybe provided in a manner such as shown in either FIG. 2A or 2B, forexample. Between the array of electrodes 320 and the skin 330 there isprovided a substance 340 to be absorbed, whereby the substance 340 hasbeen previously applied to the skin 330 (e.g., applied to the skinbetween 30 seconds to 2 minutes before the probe is to be applied to theskin 330). Application of mechanical vibrations and electrical pulsesenhances the absorption of the substance 340 into the skin 330.

FIG. 5 shows one configuration of a hand-held probe 500 that may be usedto provide both electrical and mechanical stimulation to the skin,according to one or more embodiments of the invention. The probe 500 isconfigured to be readily held by one hand of a user. A bottom portion ofthe probe 500, at which a user's hand is gripped thereon to thereby holdthe probe 500, may include an outlet 510 for coupling an electricalcable to an electrical outlet (e.g., wall outlet), so as to provide A.C.voltage to the probe 500 in that manner. Alternatively, battery powermay be used, by way of batteries (not shown) disposed within the housingof the probe 500. Battery power may be utilized when A.C. power is notreadily available. Also, the pulse generator 400 of FIG. 4 is preferablyhoused at the handle portion of the probe 500.

The head portion of the probe 500 is where the vibrating plate 130 (seeFIG. 1A or 1B) is provided, and also where the D.C. electrical motor 110(see also FIG. 1A or 1B) that provides the mechanical vibrations to thevibrating plate 130 is preferably provided housed within. The array ofelectrodes (see FIG. 2A or 2B) are provided on an outer surface of thevibrating plate 130, thereby facing the skin of a user to be treatedwith the probe 500.

A typical application time of the probe to the skin may be on the orderto 10 s of seconds up to several minutes.

In a fourth embodiment, as shown in FIG. 6, the output of the pulsegenerator 400 (see also FIG. 4) is connected to a D.C. current generator610, which induces a iontophoresis effect in addition to the previouslydescribed skin absorption/transpiration effects. The iontophoresiseffect is well known to those skilled in the art, and severalionthophoresis electrical generators are currently available in themarket, either D.C. or D.C. pulsed. A D.C. current output by the D.C.current generator 610 is applied between the electrodes of the probe anda ground plate that is connected with the patient's body. Depending onthe substance to be absorbed into the patient's skin, the patient groundplate connection is coupled to either the positive or the negative ofthe D.C. current generator 610, in a manner known to those skilled inthe art. Instead of using continuous D.C. current, there canalternatively be provided D.C. current pulses that have the same averagecurrent value as the continuous D.C. current case, and which have a dutycycle between 5 and 50% and a frequency between 10 and 5000 Hz. In sucha case, the peak current of the D.C. current pulses is higher during thepulsed (ON) times.

In a fifth embodiment, as shown in FIGS. 7 and 8, a dispenser or chamber710, which is configured to hold liquid or cream or gel 720, isintegrated in the vibrating head of the probe. The dispenser or chamber710 is provided between an array of electrodes 705 and the vibratingplate 130. The burst of electrical pulses are applied by way of aconductive roller 740 that dispenses the liquid, and by the array ofelectrodes 705. A D.C. current as in the third embodiment can also beadded between the array of electrodes 705 and the patient's body, toinduce a iontophoresis effect as well. While the vibrating head is movedon the patient's skin, the roller 740 delivers the liquid or cream orgel 720 to the patient's skin.

The chamber 710 in which the roller 740 is disposed in the vibratinghead can be filled with a liquid, cream or gel substance 720 by way of aremovable cap (not shown). In particular, the cap is removed (e.g.,screwed off of the head of the probe), and then a user fills the chamber710, through the liquid inlet 760, with the substance 720 to be providedto the patient's skin. The user then closes the cap (e.g., screws itback onto the liquid inlet 760) to thereby keep the substance 720 withinthe chamber 710 of the probe until it is ready to be applied to thepatient's skin by way of the roller 740.

FIG. 8 shows a front view of the electrodes 705, which are shown as twostripe electrodes that are electrically connected to each other by wayof electrical connection 820. Of course, other types of electrodearrays, such as those shown in FIGS. 2A and 2B, can alternatively beused in this fifth embodiment. The exposed surface 830 of the roller 740that applies the substance to the patient's skin, is shown in FIG. 8.Dispensing gaps 840 are also shown in FIG. 8, whereby these gaps 840allow the liquid, cream or gel substance 720 in the chamber 710 togradually come out of the chamber 710 and thereby be applied to thepatient's skin by way of the roller 740.

In a sixth embodiment of the invention, an apparatus for enhancingabsorption of the skin includes an array of electrodes, and a pulsegenerator that is electrically coupled to the array of electrodes. Thedisposition of the array of electrodes may be any of the dispositionsshown in FIGS. 2A-2C, for example. In a preferred implementation of thesixth embodiment, electrical pulses outputted by the pulse generator 400to the array of electrodes are a sequence of exponential pulses, such asthe pulse train shown in FIG. 4B. The exponential electrical pulses areapplied to the skin by way of the array of electrodes and are generatedby the secondary winding of a high voltage transformer with the primarywinding driven by a square wave voltage, as seen by FIGS. 4, 4A and 4B.

In the sixth embodiment, unlike the previous embodiments, a vibratinghead is not utilized, but rather skin absorption enhancement is obtainedjust by the providing of the electrical pulses to the skin by way of thearray of electrodes. The array of electrodes according to the sixthembodiment are provided on a plate at the head of the probe, whereby thehead and the plate do not vibrate. Thus, in the sixth embodiment, thestructure as shown in FIGS. 1A and 1B would not be utilized, but ratherjust a plate for holding the electrodes in place at the head of theprobe would be needed.

In a seventh embodiment, a vibrating head is utilized, as in the firstthrough fifth embodiments, but where the vibrating head is capable ofbeing turned on or off, by way of a control (e.g., switch) provided onthe probe. The control can readily be manipulated by an operator of theprobe, in order to treat a patient.

An eighth embodiment of the invention is described below, with referenceto FIGS. 9-11. FIG. 9 shows a front view of a head 800 of a probe,whereby that view shows the portion of the probe that is applied to theskin of a patient. FIG. 10 shows a section view taken along an axis ofone belt, and FIG. 11 shows a section view taken at the middle of thehead of the probe.

The eighth embodiment provides for a fairly even absorption under theskin of a substance previously applied to the skin, such as collagenpreviously applied to the skin. In the eighth embodiment, a head 800 ofa probe to be applied to the skin includes a vibrating plate 810, avacuum chamber 820, rollers 830, and belts 840 disposed around therollers 830. The rollers 830 are conductive rollers, whereby the rollers830 are electrically coupled to electrodes (see FIGS. 2A through 2C, forexample) provided on the vibrating plate 810. As in the otherembodiments, a pulse generator (see FIG. 4, for example) is electricallycoupled to the electrodes on the vibrating plate 810, in order toprovide electrical pulses to the patient's skin (by way of theconductive rollers).

In the eighth embodiment, the rollers 830 are separated from each otherby around 40 mm. Of course, other separation distances are possible,while remaining within the scope of the invention (e.g., 20 mm to 80 mmseparation). The rollers 830 are disposed at one end of the vacuumchamber 820, whereby the vacuum chamber 820 includes an opening that iscoupled to a pipe 845 that is in turn coupled to a vacuum pump 855.

When the vacuum pump 855 is operated, the vacuum chamber 820 generates asuction effect on the skin 850, thereby enabling a stronger contactbetween the rollers 830 and the skin 850, and thereby generating anadditional massaging effect to the skin 850, in addition to thevibrations generated by the vibrating plate 810. On opposite ends of therollers 830 are the belts 840, which are preferably rubber belts. Thebelts 840 are used in order to avoid direct friction between the skin850 and the body of the vacuum chamber 820.

The eighth embodiment provides good skin absorption results anddecreases the appearance of cellulite on the skin after application of asubstance for reducing cellulite is applied to the skin. Such asubstance for reducing cellulite that can be applied to the skin may bejarulon acid, for example. Such a substance could also be previouslyspread on the skin and absorbed by the skin utilizing one of thepreviously-described embodiments.

Also, while the eighth embodiment has been described as having avibrating plate, as in the first through fifth embodiments, anon-vibrating plate as in the sixth and seventh embodiments (when thevibrating plate is turned off) may be utilized in an alternativeconfiguration. In that case, the plate disposed above the vacuum chamberis non-vibrating, and contains electrodes disposed therein.

A ninth embodiment of the invention will be described in detailhereinbelow with reference to FIGS. 12-14. The ninth embodiment includesa motor 1, a screw 2, a slide 3, a frame 4, a piston 5, a syringe 6, apipe (or tubing) 7, a central electrode 8, and circumferentialelectrodes 9 (that are disposed outside of the central electrode 8) on ahead 10. The head 10 is a head portion of a probe, such a probe shown inFIG. 5 in the previous embodiments (except for the fifth embodiment,whereby the substance is disposed within a chamber within the head thatis adjacent to the electrode plate, and thus a syringe would not beneeded in that case), for example.

In the ninth embodiment, the syringe 6 is preferably a disposable,single-use syringe, which is positioned adjacent to the probe (only thehead 10 of the probe is shown in FIG. 12, whereby the rest of the probeis hidden behind the head 10 in the view provided in FIG. 12). Thesyringe 6 is inserted or fitted onto the frame 4, and does not moverelative to the frame 4. For example, the frame 4 may be placed on atable next to a bed on which a patient to be treated is located.

The piston 5 is operable to move relative to the frame 4, whereby themovement is caused by the motor 1, the screw 2, and the slide 3, whichoperate together as a moving means. With the configuration shown in FIG.12, the probe is free-standing and can be moved a certain amount (e.g.,1 to 10 feet, depending on the length of the tube 7) relative to theframe 4 (while maintaining a coupling to the syringe 6 by way of thetube 7 that couples the syringe 6 with the head 10 of the probe). Thatway, the probe can be moved around to treat different areas of a skin ofa patient lying on a bed, while the frame containing the syringe 6 restsin place on a table next to the bed. In an alternative configuration,the probe and the syringe 6 can both be mounted on the frame 4, as asingle-block construction. In this configuration, the entire frame ismoved to different areas of the patient's skin, to thereby treat thepatient by way of a probe that is inserted in the frame. The head of theprobe extends out from one end of the frame, so that it can be placedagainst the patient's skin.

In a preferred implementation, the motor 1 is powered by a differentpower source than the source providing power to the probe. However, in adifferent implementation, the motor 1 and the probe may be powered bythe same power source.

A tube or pipe 7 is used to connect the syringe 6 with the head 10 ofthe probe. The tube 7 is preferably a disposable, single-use component,and may be a flexible plastic tubing, for example. The head 10 ispreferably a vibrating head, such as described earlier with respect toother embodiments. In an alternative configuration, the head 10 does notvibrate, and only electrical pulses are provided to the skin (so as toelectroporate the skin to thereby absorb the substance provided to theskin by way of the syringe 6 and tube 7) in this alternativeconfiguration. The tube 7 is preferably 0.5 to 3 millimeters indiameter, and is sized so as to allow a liquid or cream-like substanceto flow through the tube 7, and exit the tube 7 at a second end oppositea first end of the tube 7 that is coupled to the syringe 6. Such asubstance to be applied to the skin may include water-based collagen,water-based elastine, and anesthetic, or other type of drug, just toname a few.

Referring now to FIG. 14, the tube 7 couples to the head 10 by way of agroove 12 that is located at an end of the head 10 and that is providedall the way to a groove 11 that surrounds the central electrode 8. Thegroove 12 is sized so as to accept the tube 7 fitted therein to providea snug fit, whereby the tube 7 is preferably fitted within the groove 12by feeding the tube 7 within the groove 12 from the end of the head 10where one end of the groove 12 is disposed. In the ninth embodiment, thesize of the groove 12 is such that the tube 7 does not extend above theupper surface of the head 10 (where the electrodes 8, 9 are disposed),or whereby the tube 7 extends slightly below the upper surface (plate)of the head 10. That way, the tube 7 will not be felt by the patientwhen the head 10 of the probe is moved along the skin of the patientduring a treatment. Preferably, the tube 7 will not be in contact withthe skin of the patient during treatment of the patient by way of amethod and/or apparatus according to the ninth embodiment. The topsurface of the head 10 preferably has a plate-like configuration, so asto provide a smooth feeling to the patient's skin.

On the top surface of the head 10 there are provided one centralelectrode 8 and a plurality of circumferential electrodes 9 disposedaround the central electrode 8. The groove or trough 11 surrounding thecentral electrode 8 is preferably 1 mm wide, whereby the groove 11 iscoupled to one end of the groove 12 in which a portion of the tube 7 isdisposed. That way, when a substance is flowed out of the syringe 6 (byway of action by the motor 1, the screw 2 and the slide 3), thesubstance flows through the tube 7 (disposed within the groove 12) andthereby into the groove 11. The substance collects within the groove 11surrounding the central electrode 8, and is absorbed by the skin duringan electroporation treatment (using electrical pulses and mechanicalvibrations) by way of the ninth embodiment. When the top surface (plate)of the head 10 is placed in contact with the patient's skin, thesubstance within the groove 11 comes into contact with the patient'sskin, and is absorbed by the skin.

Although eight circumferential electrodes 9 are shown in FIG. 12, theinvention according to the ninth embodiment can operate with differentnumbers of circumferential electrodes 9. For example, a minimum of twocircumferential electrodes 9, disposed opposite from each other (withthe central electrode 8 disposed therebetween), may be utilized in adifferent configuration. Also, four circumferential electrodes 9 andmore than eight circumferential electrodes 9 may be utilized in otherdifferent configurations (e.g., 16 electrodes, 32 electrodes, or an oddnumber, such as three, five, or seven, circumferential electrodessurrounding the central electrode 8) of the ninth embodiment.

A pulse generator, such as the one shown in FIG. 4 (see also FIGS. 4Aand 4B), is used to provide electrical pulses to the electrodes 8, 9disposed on the head 10 of the probe. As explained earlier, thepreferred shape of the electrical pulses is an exponential shape, asshown in FIG. 4B. Alternatively, sinusoidal or sawtooth waveforms may beprovided, but exponential pulses provide a better skin transpirationeffect. Operation of the pulse generator that may be utilized in theninth embodiment has been described in detail with respect to the firstembodiment described previously, and will not be described here for sakeof brevity.

One of the two outputs of the pulse generator (see FIG. 4) is connectedto the central electrode 8, and the other of the two outputs of thepulse generator is connected to one of the circumferential electrodes 9.The circumferential electrodes 9 are coupled to each other electricallyon the back side of the head (see dashed line in FIG. 2C), so that eachof the electrical pulses provided on the other of the two outputs of thepulse generator is provided to all of the circumferential electrodes 9simultaneously.

The voltage of the electrical pulses provided to the skin from each ofthe eight circumferential electrodes 9 can be considered as a “ground”with respect to the voltage of the electrical pulse provided to the skinfrom the one central electrode 8. Since the central electrode 8 carriesmore electrical current than each of the eight circumferentialelectrodes 9, the circumferential electrodes 9 act like a groundconnection, whereby the electrical current carried by each of the eightcircumferential electrodes 9 is approximately eight times less than theelectrical current carried by the central electrode 8.

The piston 5 of the syringe 6 is moved by the motor 1, which is a DCelectric motor in a preferred implementation. The motor 1 is connectedto the screw 2, which moves the piston 5 by way of the slide 3 that isattached to the screw 2 at a particular location on the screw 2. Whenthe head 10 of the probe is positioned on a patient's skin, electricalpulses are delivered to the electrodes 8, 9, and the piston 5 of thesyringe 6 is moved by the motor 1 in order to deliver the liquid orcream-like substance (or drug) from within the syringe 6 to thepatient's skin. The liquid, cream or drug is preferably provided to thepatient's skin in a slow, controlled manner, to allow the substance tobe properly absorbed within the skin. For example, a water-basedcollagen, a water-based elastine, an anesthetic, or other type of drugmay be provided within the syringe 6, to then be provided to the skin ofa patient (to be absorbed therein) by way of the method and apparatusaccording to the ninth embodiment.

The enhancement of the skin absorption by electrical pulses applied tothe skin, and also by mechanical vibrations applied to the skin at thesame time in a synchronous manner (see description of the vibratingplate with respect to other embodiments) of the ninth embodiment,enables the absorption of a drug or other type of substance delivered byway of the syringe 6. A typical drug absorption quantity is 1 cubiccentimeter in one to five minutes, by using the method and apparatusaccording to the ninth embodiment. In this regard, the timing of themovement of the piston 5 is such that the correct amount of substance isoutput from the syringe 6 during a treatment of a patient, whereby whenthe probe is turned on, this event will provide a trigger signal to themotor 1 to start to operate. Operation of the motor 1 will in turn causethe substance within the syringe 6 to be pushed out of the syringe 6,and into the groove 12 surrounding the central electrode 8.

The substance is introduced within the syringe at a previous time, sothat the syringe 6 with the substance provided therein can then beattached to the frame 4, coupled to the tube 7, and thereby provide anapparatus that can introduce drugs and/or other substances to the skinof a patient, by way of a probe having a head 10 with electrodes 8, 9provided on an outer surface or plate of the head 10. As explainedearlier, the head 10 vibrates, so that both electrical and mechanicalvibrations are provided to the patient's skin at a same time the drug orother substance is provided to the patient's skin (by way of thesubstance disposed within the trough or groove 12 being in contact withthe patient's skin during a treatment of the patient). In an alternativeconfiguration, which provides a skin transpiration effect not as good asusing both mechanical vibrations and electrical pulses, only electricalpulses are provided to a patient's skin (the head does not vibrate).This configuration is cheaper to build, and may be suitable for certaininstances.

The motor 1, screw 2, slide 3, piston 5, syringe 6, frame 4 and tube 7may be coupled to different types of probes, in order to provide anapparatus for skin absorption enhancement and transdermal drug delivery.For example, any of the probes described with respect to the otherembodiments (except those that have the substance stored in a containerwithin the head of the probe) may be utilized with the componentsdescribed above. Also, the structure for moving a substance out of thesyringe 6 may be accomplished by ways other than the screw/slide/motor“moving means” described with respect to FIG. 12, while remaining withinthe scope of the invention.

FIG. 13 shows a back view of the head 10, whereby components used tocouple the electrodes 8, 9 to the head and to provide an electricalconnection to the electrodes 8, 9 are also shown in FIG. 13. A motor1310, which includes an eccentric 1320 coupled to an output of the motor1310, is used to provide mechanical vibrations to the head 10, so thatthe apparatus provides both electrical and mechanical vibrations to apatient's skin at the same time. These mechanical vibrations arepreferable synchronized with the electrical pulses, as described earlierwith respect to other-described embodiments of the invention.

The electrodes 8, 9 are preferably screwed onto the front plate of thehead 10. Washers 1330 and screws 1340 are utilized to electricallycouple wires 1350, 1355 to the electrodes 8, 9. In particular, wire 1350(that has one end coupled to one of the two outputs of the pulsegenerator as shown in FIG. 4, for example) is electrically connected tothe central electrode 9, and wire 1355 (that has one end coupled to theother of the two outputs of the pulse generator as shown in FIG. 4, forexample) is electrically connected to the circumferential electrodes 8.Resistor 1365 is provided between the wires 1350, 1355, in the preferredconstruction. Also shown in FIG. 13 is a housing 1375 which is coupledto the head 10 by way of screws 1380. The eccentric 1320 moves withinthe housing 1375, thereby causing vibrations that are translated to thehead 10 of the probe.

A tenth embodiment of the invention will be described herein withrespect to FIGS. 15 and 16. The tenth embodiment is similar to the ninthembodiment, but utilizes a different configuration for the head, as wellas providing a plurality of transformers (see FIGS. 4, 4A and 4B). FIG.15 shows a back view of the electrodes 1500 disposed on a head 1510 of aprobe, and FIG. 16 shows a front (skin-side) view of the electrodes1500, whereby each electrode has a groove or trough 1530 surrounding it.Each groove 1530 has an outlet that extends to an edge of the head 1510,to thereby allow a respective tube 1550 to be fitted therein, so as toprovide an amount of substance from the syringe 6 to the grooves 1530.That way, the tubes 1550 do not extend above the top surface of the head1510. As an alternative to the multi-port tube configuration shown inFIG. 16, a number of syringes equal in number to the number ofelectrodes may be provided, with a tube provided to couple a syringe toan electrode.

In the tenth embodiment, each electrode 1500 is active and is connectedto its own pulse transformer 1560A-1560I. The substance from the syringe6 is provided to grooves 1530 surrounding each of the electrodes 1500.The electronic pulses are provided to each of the electrodes 1530 fromthe respective pulse transformers 1560A-1560I, whereby transformers1560C, 1560E, 1560G and 1560I provide positive pulses to theirrespective electrodes, and whereby transformers 1560A, 1560B, 1560D,1560F and 1560H provide negative pulses to their respective electrodesat the same time, for the nine electrode configuration. Moreparticularly, transformers 1560C, 1560E, 1560G and 1560I have theirprimary and secondary windings connected in phase, and transformers1560A, 1560B, 1560D, 1560F and 1560H have their primary and secondarywindings connected 180 degrees out of phase (see oppositely-positioneddots for those transformers in FIG. 15). If a square wave is applied toall of the primary windings of the transformers at the same time andwhen there is a positive transition from low to high, the transformerswith their primary and secondary windings in phase with each other willoutput a positive exponential pulse, and the transformers with theirprimary and secondary windings 180 degrees out of phase with each otherwill output a negative exponential pulse.

In the tenth embodiment, it is preferable that a first group ofelectrodes receive a positive pulse at a same time a second group ofelectrodes (equal or nearly equal in number to the first group,preferably) receive a negative pulse, to provide a good skintranspiration effect. The type of pulses, the burst duration, thefrequency, etc., are similar to the embodiments described earlier. Also,the tenth embodiment may include a mechanical vibration that is appliedto the patient's skin at the same time the electrical pulses are appliedto the patient's skin, in a manner described previously.

In an eleventh embodiment, a plurality of transformers are respectivelyprovided to output electrical pulses to a plurality of electrodesdisposed on a head portion of a probe, whereby the plurality oftransformers provide separate and independent pulse bursts to theirrespective electrodes. For example, each of the pulse generators in theeleventh embodiment may have different phase shift amounts within arange of from 0 degrees to 360 degrees. In this regard, the outputpulses from the transformers are synchronized with each other, to have aparticular out-of-phase relationship with respect to each other.

One example of an electrode array according to the eleventh embodimentis shown in FIGS. 17, 18 and 19. This example provides a three electrodeconfiguration, with no central electrode. Referring now to FIG. 17,which shows a front side of the head 10, electrodes 1700 arerespectively coupled via tube 1710 to a syringe 6, to receive asubstance in a groove 1720 surrounding each of the electrodes 1700. Likethe previously-described embodiments, as shown in FIG. 14, a groove orpath to an end of the head 10 is provided, in order to fit the tube 1710snugly within it so that the tube 1710 does not extend above the uppersurface (plate) of the head 10 that makes contact with a patient's skin.

Referring now to FIG. 18, which shows a back side of the head 10,transformers 1810A, 1810B and 1810C respective provide pulses of thesame polarity, but delayed from each other by a particular amount, tothe corresponding one of the electrodes 1700 coupled to eachtransformer. FIG. 19 shows the input square wave pulses that areprovided to each transformer, whereby the square wave pulses that areinput to transformer 1810C are delayed a certain amount (e.g., 30degrees) with respect to the square pulses that are input to transformer1810B, which in turn are delayed a certain amount (e.g., 30 degrees)with respect to the square wave pulses that are input to transformer1810A. This can readily be done by providing the trigger “IN” signal toeach of the respective transformers 1810A, 1810B, 1810C at theappropriate timings. The result are exponential pulses that are outputfrom each of the three pulse generators, whereby the exponential pulsesare phase-shifted a fixed amount with respect to each other.

With the three-electrode and three-pulse-generator configuration asshown in FIGS. 17-19, it is possible to provide a 120 degree phase shiftwith respect to the signals output by the three pulse generators (e.g.,one signal output at 0 degrees, one signal output at 120 degrees, andone signal output at 240 degrees). This provides a rotation of theelectric field between the electrodes 1700 in a manner similar to whathappens with a rotation of a three-phase motor. More generally, in theeleventh embodiment, using a number “n” of electrodes and “n” pulsegenerators, one of ordinary skill in the art will understand that onecan devise any particular type of electric field distribution on theskin surface to be treated by way of an apparatus according to theeleventh embodiment, as desired.

Experimental results of the application of the several embodiments ofthe skin absorption apparatus described hereinabove to the skindemonstrated that a noticeable variation of results and rate ofabsorption of substances occurred. The analysis was carried out over anarea of skin previously dermabraded with a standard microdermabraderavailable on the market and an adjacent area not previously dermabraded.This analysis demonstrated that the results obtained in the dermabradedarea are fairly constant and reproducible while the results in thenon-dermabraded area are variable and somewhat inconsistent. Thisinconsistency is due to the fact that the stratum corneum (also referredto as the horny or dead outermost layer of the epidermis) of the skinacts like a barrier to the absorption of the substances applied to theskin, and moreover it increases the electrical resistance of the skin,thereby somewhat decreasing the absorption effect of the skin absorptiontreatment according to the invention.

The thickness of the stratum corneum is variable from person to person,and moreover it is variable from time to time in the same person. Thisinduces a variability that makes it difficult to come up with a standardapplication time of the skin absorption apparatus according to thevarious embodiments of the invention. For this reason, according to yetanother embodiment of the invention, a skin absorption treatment methodincludes a microdermabrasion performed before the application of theskin absorption apparatus in order to give more reproducible and moreconstant results as compared to the embodiments in which amicrodermabrasion is not first performed. The microdermabrasion to beperformed prior to the skin absorption treatment may be one described invarious U.S. patents assigned to Mattioli Engineering, Ltd., such asU.S. Pat. Nos. 6,322,568 and 6,039,745, each of which are incorporatedin their entirety herein by reference, or other types of dermabrasiontreatments conventionally known.

Preferably, the dermabrasion treatment is performed for three minutes inorder to remove a 100 micron layer of the corneum status of the skin inan area to be later treated with a skin absorption enhancement deviceaccording to one of the embodiments of the invention. Ideally, the skinabsorption treatment is performed soon after (e.g., within 5 minutes) ofthe completion of the dermabrasion treatment. Of course, other timelengths of dermabrasion treatment, depth of corneum status removal, andtime between the dermabrasion treatment and the skin absorptiontreatment, may be contemplated while remaining within the scope of theinvention as described hereinabove.

Different embodiments of the present invention have been describedaccording to the present invention. Many modifications and variationsmay be made to the techniques and structures described and illustratedherein without departing from the spirit and scope of the invention.Accordingly, it should be understood that the apparatuses describedherein are illustrative only and are not limiting upon the scope of theinvention.

What is claimed is:
 1. A treatment method for enhancing absorption ofsubstances provided on a skin surface of a patient, comprising: a)applying a substance within a syringe; b) applying a sequence of burstsof electrical pulses to an array of electrodes that are placed a regionof the skin, the array of electrodes being disposed on a head of aprobe; and c) at the same time as step b), causing the substance to beoutput from the syringe and onto the head of the probe, in a controlledmanner, wherein the sequence of bursts of electrical pulses are providedto the region of the skin in order to enhance absorption of thesubstance applied to the region of the skin, wherein the electrodes areround electrodes with one central electrode and a plurality ofnon-central electrodes disposed around the central electrode, whereinone electrical pulse is provided solely to the one central electrode,and wherein another electrical pulse is provided to the plurality ofnon-central electrodes that are electrically connected to each other butnot to the one central electrode.
 2. The treatment method according toclaim 1, further comprising: d) at a same time as step b) and step c),applying a mechanical vibration to the region of the skin of between 10to 200 Hz, the mechanical vibration being provided by vibrating the headof the probe.
 3. The treatment method according to claim 1, wherein aD.C. current is applied between the electrodes and a ground plateconnected to the patient.
 4. The treatment method according to claim 1,wherein the sequence of pulses are provided at a frequency between 50 to15,000 Hz and peak voltage between 20 and 200 V.
 5. The treatment methodaccording to claim 1, further comprising: prior to step a), performing adermabrasion on the region of the skin.
 6. An apparatus for enhancingabsorption of substances provided on a skin region of a patient,comprising: an array of electrodes provided on a head of a probe; asyringe that is configured to hold the substance to be provided on theskin region of the patient; a frame in which the syringe is fixedlymounted; a pulse generator configured to generate a sequence of burstsof electrical pulses to the array of electrodes that are placed on theskin; and moving means for moving a piston of the syringe so as tooutput a particular amount of the substance from the syringe and ontothe head of the probe at a particular rate, wherein the sequence ofbursts of electrical pulses are provided to the skin region by way ofthe array of electrodes at the same time the outputting means is causingthe substance to be output from the syringe, in order to enhanceabsorption of the substance applied to the skin region when the head ofthe probe is placed against the skin region of the patient, wherein thearray of electrodes comprises: a central electrode; and a plurality ofnon-central electrodes disposed around the central electrode, wherein agroove is provided only around the central electrode and not around saidplurality of non-central electrodes in order to accept the substanceoutput from the syringe.
 7. The apparatus according to claim 6, whereinthe electrical pulses are output at a frequency between 50 to 15,000 Hzand peak voltage between 20 and 200 V.
 8. The apparatus according toclaim 6, wherein the moving means comprises: a motor; an output rodcoupled to the motor and configured to rotate when the motor operates;and a slide coupled to one end of the output rod, wherein the slide isdisposed against the piston of the syringe, and operates to push thepiston inwards when the motor operates.
 9. The apparatus according toclaim 6, further comprising: a tube that couples the syringe to thegroove wherein the tube is adapted to fit within a trough provided onthe head of the probe to thereby have an end of the tube providedadjacent to the groove, wherein the substance flows from the syringe andinto the groove by way of the tube.
 10. The apparatus according to claim6, further comprising: a motor; and an eccentric for receiving outputfrom the motor and for providing an eccentric force to the head of theprobe, the eccentric force causing mechanical vibrations of the headwhich are translated to the skin of the patient when the head of theprobe is in contact with the skin of the patient.
 11. The apparatusaccording to claim 10, further comprising: a controller forsynchronizing the mechanical vibrations with the electrical pulses suchthat a vibration frequency of the mechanical vibrations isfrequency-synchronous with a burst frequency of the sequence of burstsof electrical pulses.
 12. An apparatus for enhancing absorption ofsubstances provided on a skin region of a patient, comprising: an arrayof electrodes provided on a head of a probe; a syringe that isconfigured to hold the substance to be provided on the skin region ofthe patient; a frame in which the syringe is fixedly mounted; a pulsegenerator configured to generate a sequence of bursts of electricalpulses to the array of electrodes that are placed on the skin; movingmeans for moving a piston of the syringe so as to output a particularamount of the substance from the syringe and onto the head of the probeat a particular rate; a plurality of electrodes disposed a particulardistance from each other; a plurality of grooves respectively providedon a one-to-one basis around the plurality of electrodes; and aplurality of tubes respectively provided on a one-to-one basis for saidplurality of electrodes and configured to provide the substance to saidplurality of grooves for application to the skin region of the patient,wherein said plurality of tubes are connected at one end to said syringeand at an opposite end to a respective one of said plurality ofelectrodes, and wherein the sequence of bursts of electrical pulses areprovided to the skin region by way of the array of electrodes at thesame time the outputting means is causing the substance to be outputfrom the syringe, in order to enhance absorption of the substanceapplied to the skin region when the head of the probe is placed againstthe skin region of the patient.
 13. An apparatus for enhancingabsorption of substances provided on a skin region of a patient,comprising: an array of electrodes provided on a head of a probe; asyringe that is configured to hold the substance to be provided on theskin region of the patient; a pulse generator configured to generate asequence of bursts of electrical pulses to the array of electrodes thatare placed on the skin; a vibrating unit configured to providemechanical vibrations to the head of the probe; and a pipe that isconfigured to provide the substance from the syringe to the head of theprobe, wherein the sequence of bursts of electrical pulses and themechanical vibrations are provided to the skin region at the same timethe substance is provided to the head of the probe in a frequencysynchronous manner such that a frequency of application of the bursts ofelectrical pulses is a same as a frequency of application of themechanical vibrations, in order to enhance absorption of the substanceapplied to the skin region when the head of the probe is placed againstthe skin region of the patient.
 14. The apparatus according to claim 13,wherein the array of electrodes comprises: a plurality of electrodesdisposed a particular distance from each other, wherein a groove isprovided around at least one of the electrodes in order to accept thesubstance output from the syringe.